Dressing up amino acids by adding new substituent groups to them can introduce novel catalytic and medicinal properties. Adding a methyl group to tryptophan’s β carbon, however, has proven difficult and inefficient. A research team has now used directed evolution to produce an enzyme that catalyzes the synthesis of β-methyltryptophan analogs in just one step (J. Am. Chem. Soc. 2016, DOI: 10.1021/jacs.6b04836). Andrew R. Buller, Frances H. Arnold, and colleagues at California Institute of Technology discovered that a subunit of tryptophan synthase can construct β-methyltryptophan from indole and the amino acid threonine, but the activity was weak. So they randomly mutated the enzyme, looked for mutants with increased production of β-methyltryptophan, and then recombined genes coding for the most active variants. The researchers ended up with an enzyme that had eight mutations and was 1,000 times as active in making β-methyltryptophan as the natural tryptophan synthase. Incorporating substituted indoles led to a whole family of β-branched tryptophans.